EFFICACY AGAINST PARASITES

Efficacy against a specific parasite depends on the delivery form and on the dose administered.

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DOSING

Click here to view the article in this site with the most common dosing recommendations for mebendazole used in domestic animals.

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SAFETY

Oral LD50, rat, acute*: 714-1434 mg/kgDermal LD50, rat, acute*: not found* These values refer to the active ingredient. Toxicity has to be determined for each formulation as well. Formulations are usually significantly less toxic than the active ingredients.

MRL (maximum residue limit) established for either beef, mutton pork or chicken meat*:

CODEX: No

EU: Yes

USA: No

AUS: Yes

* This information is an indicator of the acceptance of an active ingredient by the most influential regulatory bodies for use on livestock.

SPECIFIC FEATURES

Mebendazole is a veteran anthelmintic (wormer) compound belonging to the chemical class of the benzimidazoles. Mebendazole is moderately used in pigs, dogs ans cats. It is very scarcely used in ruminants. It is vastly used in horses.

Mebendazole is absorbed slowly in the stomach. Therefore the longer it remains there, the better the efficacy. In carnivores (e.g. dogs and cats) and other animals with a simple stomach the passage through the stomach is rather fast and therefore a higher dosage or repeated treatments are usually required.

Mebendazole has no residual effect. This means that a single administration will kill the parasites present in the host at the time of treatment, but it will not protect against re-infestations.

At the therapeutic dose mebendazole is not effective against flukes and whatsoever external parasites.

Resistance of worms to benzimidazoles, including mebendazole in dogs, cats, pig and poultry is not a problem so far. However resistance of several gastrointestinal roundworms to all benzimidazoles, including mebendazole is already very high and very frequent worldwide in sheep and goats, slightly lower in cattle. For this reason, the risk that benzimidazoles fail to protect ruminants against gastrointestinal roundworms is considerable worldwide.

Pharmacokinetics of mebendazole

Mebendazole is very poorly soluble in water. Orally administered mebendazole is poorly absorbed into the bloodstream: ~30% in pigs, and <10% in dogs. This means that significant amounts remain in the gastrointestinal tract and are available for the control of gut dwelling roundworms and tapeworms.

Absorbed mebendazole is quickly broken down in the liver to metabolites without anthelmintic efficacy. Both the parent molecule and its metabolites are excreted mainly through bile and feces, the rest through urine. However, there are important species-specific differences. Whereas in dogs >90% of the administered dose is excreted through feces, up to 50% is excreted through urine in swine.

Influence of parasites. Heavy liver fluke infestations in sheep slow down the metabolism of mebendazole in the liver, which increases its bioavailability and prolongs the residence time. This may require longer withholding periods.

Mechanism of action of mebendazole

The molecular mode of action of all benzimidazoles, including mebendazole, consists in binding to tubulin, a structural protein of microtubules. These microtubules are important organelles involved in the motility, the division and the secretion processes of cells in all living organisms. In the worms the blocking of microtubules perturbs the uptake of glucose, which eventually empties the glycogen reserves. This blocks the whole energy management mechanism of the worms that are paralyzed and die or are expelled.

Since cell division is also disturbed, worm egg production and development is also blocked by benzimidazoles, i.e. most of them also have an ovicidal effect.

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